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For Chronic GVHD, Second-Line Therapies Vary Widely

A retrospective analysis of Canadian cases finds clinicians turn to a variety of therapies for chronic graft-vs-host disease (GVHD) if corticosteroids fail.

A new review of chronic graft-vs-host disease (cGVHD) cases suggest there is an unmet need for more effective treatment options for patients whose initial treatment fails.

The review, based on cases at 7 treatment sites across Canada, was published in Transplantation Proceedings.

Between 30% and 50% of patients who undergo allogeneic hematopoietic cell transplant (HCT) will experience cGVHD, which typically appears more than 100 days after the transplant, according to the authors. Complications from cGVHD can affect a variety of parts of the body, including the skin, joints, liver, and gastrointestinal tract, they noted, all leading to significant morbidity and higher rates of health care utilization.

Complications from cGVHD can affect a variety of parts of the body, including the skin, joints, liver, and gastrointestinal tract. | Image Credit: © andrii - stock.adobe.com

Complications from cGVHD can affect a variety of parts of the body, including the skin, joints, liver, and gastrointestinal tract. | Image Credit: © andrii - stock.adobe.com

The standard first-line therapy for such patients is steroids, with or without calcineurin inhibitors, the authors said. However, the options are more diverse if corticosteroids fail. Immunosuppressive medications have long been used, although the authors wrote that the data to support their use is lacking. More recently, drugs such as ruxolitinib (Jakafi; Incyte), ibrutinib (Imbruvica; Pharmacyclics/Janssen), and belumosudil (Rezurock; Kadmon) have been approved for cGVHD, but the investigators said their influence in real-world settings remains unclear.

“Studies comparing the efficacy of different second-line treatment options for cGVHD are lacking and there is still no standard of care for later-line treatment for steroid-refractory cGVHD,” they wrote.

In hopes of better understanding how patients with cGVHD are being treated after first-line therapy, and how those treatments are impacting patient outcomes, the investigators retrospectively examined adult patients who experienced cGVHD following HCT and received systemic treatment. They identified a total of 77 cases to review; those patients had a median age of 51 years and 51% of participants were female, the authors reported. To qualify for inclusion, the patient’s HCT procedure had to have occurred at least 18 months prior to data collection.

Of those 77 patients, 59 remained on active systemic treatment at the time of data collection, 17 were on nonsystemic treatment after complications resolved, and 1 patient had died.

The investigators found that patients commonly received multiple treatments. The median number of treatment lines was 2, but nearly 40% of patients (39%) had more than 2 lines of treatments.

Among patients who remained on active systemic treatment, the investigators said the most common treatments in use were corticosteroids and ruxolitinib. However, the timing of the usage differed. All but one patient was given corticosteroids as first-line therapy, the authors said, but ruxolitinib was the most common second- and third-line treatment.

Overall, the investigators said treatment failure was common, especially in patients with lung complications or scleroderma. Among the 24 patients with lung complications, 41% had 3 or more lines of therapy. Among those with scleroderma (22 patients), 77% had received 3 or more lines of therapy, and 23% of those had received at least 6 different therapies.

The authors concluded that the data show that more work is needed to expand the treatments available to patients with cGVHD.

“Despite the variety of treatments available for physicians for management of cGVHD, the treatment options for cGVHD may not currently address all patient demands,” they wrote.

The authors added that despite the relative success of ruxolitinib in treating cGVHD, it is also associated with a higher incidence of thrombocytopenia and anemia.

As evidence of the unmet need, they noted that the patients in the study accounted for a total of 38 hospitalizations during the study period (some patients were hospitalized multiple times, they noted). The median length of hospitalization was 10 days.

The authors concluded that the variety of therapies utilized after first-line therapy and the high number of therapy lines used by patients with lung and scleroderma complications is evidence that more work needs to be done to treat cGVHD.

“Current treatment options fail to adequately control cGVHD complications for most patients resulting in high morbidity and a significant burden on the health care system,” they wrote. “New treatments with fewer serious adverse effects are needed to manage cGVHD, particularly for patients with scleroderma or lung involvement.”

Reference

Kim D, Taparia M, Robinson E, Mcgee M, Merali T. Navigating the complexity of chronic graft-vs-host disease: Canadian insights into real-world treatment sequencing. Transplant Proc. Published online February 10, 2024. doi:10.1016/j.transproceed.2023.12.021

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